The role of canine neutrophil elastase in the etiology of experimental emphysema in the dog will be determine. Purified enzyme will be instilled into the dog lungs in vivo and in vitro. The route of penetration of the neutrophil elastase from the alveolar epithelial surface to the interstitial elastin will be established using a combination of electron microscopic and immunologic techniques. The substrate specificity of neutrophil elastase and the types of hydrolysis products formed during digestion of amorphous and microfibrillar elastin will be determined by standard biochemical techniques. The role of proenzyme activation and proteinase: antiproteinase complex formation in the regulation of neutrophil elastase activity will be analyzed by in vitro studies. The sources of various lung antiproteinases will be established using isotopic labelling and some fluorescent antibody procedures. The role of altered antiproteinase (natural or synthetic) levels, in the circulation or in the lung, will be analyzed. If reduced levels of antiproteinase lead to increased susceptibility to neutrophil elastase induced emphysema, potential therapeutic models can be developed.